The present invention relates to a fused antigen polypeptide wherein two or more antigen polypeptides are fused (referred to as "hybrid antigen polypeptide" hereinafter) and a process for producing the hybrid antigen polypeptide by using a microorganism carrying a recombinant DNA containing a DNA coding for the hybrid antigen polypeptide. Antigen-antibody reaction is applied to various fields of medical care and medical science and the hybrid antigen polypeptide of the present invention is expected to be useful in a wide field.
So far, antigen-antibody reaction has been used in various fields, specifically in the field of medical treatment such as diagnosis, therapy and prevention of diseases. The usefulness of antigen-antibody reaction is due to its high specificity which assures correctness of diagnosis and effectiveness of therapy and prevention of diseases. On the other hand, it has been known that a disease is sometimes caused by plural antigen moieties. In such case, since diagnosis, therapy and prevention of the disease using one antigen moiety lead to low correctness and effectiveness due to the high specificity of antigen-antibody reaction, a mixture of two or more antigen moieties or a crude extract of pathogen has been used hitherto.
Prior art is explained in detail below by the example of serum diagnosis of adult T cell leukemia (referred to as ATL hereinafter).
Adult T cell leukemia virus (referred to as ATLV hereinafter) which is a synonym of human T cell leukemia virus (HTLV-I) is considered to be the causative virus of ATL. Serum diagnosis of ATLV infection is an important clinical diagnostic technique for the diagnosis of ATL and prevention of ATLV infection through blood transfusion, etc. Serum diagnosis is carried out by examining the presence of antibodies (referred to as anti-ATLA antibody hereinafter) to ATL-associated antigens (referred to as ATLA hereinafter) using antigen-antibody reaction. ATLA is a component of an ATLV particle and plural species of ATLA are known. They are divided into two large groups, i.e. ATLA group encoded by gag gene of ATLV and that encoded by env gene of ATLV. Further, each ATLA group contains plural species of ATLA different in antigenicity [Hattori et al., Virology, 136, 338-347 (1984)]. One anti-ATLA antibody reacts specifically with only one ATLA. It is known that various anti-ATLA antibodies are present in the serum of a person infected with ATLV and the antibodies vary with the individual. In such serum diagnosis, a method using a crude extract of ATL-derived cultured cells as an antigen has been tried. However, the method has various problems, for example, the high cost of cell culture, the safety problem involved in mass production of ATLV-excreting cells, limited productivity, etc. Further, the method leads to deletion of a sugar protein of a molecular weight of 46,000 daltons in the antigen polypeptide encoded by env gene.
On the other hand, recently a method for producing ATLA polypeptide encoded by gag gene or env gene of ATLV using a microorganism has been developed [K. P. Samuel et al., Science 226, 1094-1097 (1984); Kiyokawa et al., Proc. Natl. Acad. Sci. USA 81, 6202-6206 (1984); Sekine et al., Nippon Nogeikagaku Kai (The Agricultural Chemical Society of Japan) Summary of lectures in the 1984's meeting, page 440; Itamura et al., Summary of the 57th meeting of Nippon Seikagaku Kai (The Japanese Biochemical Society) in 1984, page 1079]. The ATLA polypeptide produced by the method has an antigenicity only as the ATLA encoded by gag gene or env gene and it is difficult to conduct correct diagnosis by using the single ATLA polypeptide. Therefore, use of a mixture of two ATLA polypeptides has been recommended. However, separate production of two polypeptides and use of a mixture thereof are economically disadvantageous.